BIOB51 Lecture 7 and 8 Final Exam Notes UTSC evolutionary Biology

BIOB51 – Lecture 7 Variation and Mutation:


• What happens after a period of strong natural selection?
o After time, natural selection is expected to reduce heritable variation in
populations because it removes unfavorable variants o Evolution cannot occur without heritable variation
• Historical view:
o Natural selection would eliminate most variation in populations
o There is little variation in current populations since evolution is considered to be
part of the past
o However, mutation is constantly making new variants
Sources of Phenotypic Variation:
1. Genetic: differences in phenotype due to differences in individual’s genotype
o Genetic variation can occur in types of encoded proteins, amount, timing, or
location of expression
o For example, in humans the TAS2R38 gene
▪ There are 2 alleles for this gene: AVI and PAV alleles

• They affect the ability to perceive bitterness in food
  
• PAV is directly related to bitterness and toxins of food
  
• AVI is related to non-tasters
  

o This type of variation can evolve since
o The internal and external environment are important for the development of most
traits.

• ▪  Genes form proteins, which make phenotypes
  
• ▪  The genes need to have the correct amino acids and enzymes.
  
• ▪  The proteins may need other proteins and the pH will have to be at a
  particular temperature for the protein to fold
  
• ▪  Also, other genes and proteins may affect the phenotype
  
• ▪  The external environment, such as temperature and other biotic and abiotic
  factors, can also affect the phenotype
  

o Phenotypes of individuals can be different even if they have identical genotypes
▪ This is because of the complexity of the gene and phenotype process
2. Environmental: differences in phenotype are due to differences in external surroundings or conditions experienced by individuals

o For example, monozygotic twins, who were formed from a single ovum. ▪ They are genetically identical but one of them is a smoker
• Despite the fact that they are genetically identical, they have different phenotypes because of environmental influences (smoking)
o Another example is of the effect of UV rays on one side of the face
▪ The man was a truck driver who had sun damage on one side of his face,
which caused that side to age faster than the other side of the face. o Another example is of inducible defenses in Daphnia (“water flea”)
▪ Some Daphnia which are genetically identical are placed in a pond with no predators, and others are in a pond with predators. The individuals who have predators grow different morphological traits to defend themselves, such as spikes.
o Environmental variation cannot evolve because there is no change in the gene sequence. Thus, changes in individuals due to the environment aren’t passed onto their offspring
3. Genotype by Environmental Interaction: Differences in phenotype due to differences in the effect of external conditions on individuals with different genotypes
o These can go to the extent to which different genotypes show different degrees of phenotypic plasticity, which is the development of different phenotypes from the expression of the same genotype in different environments.

▪
▪

For example, burning or tanning after sun exposure
• The genotype of the skin hasn’t changed, but the production of
melanin has changed due to the exposure of the sun
o People who get burnt and their skin turns red have more
susceptibility of getting cancer
o Those individuals who get tanned, the melanin of their skin
is protecting them
Another example is of Knotweed Persicaria maculosa morphology in response to light

• The number of leaves varies with light intensity
  o The more intense the light, the more leaves are produced on
  average
  
• Each line of the graph is a different genotype
  

o The slopes of the relationships are different
o This type of graph is called the norm of reaction, which is
when the graph shows variation in the phenotypes expressed by different genotypes across variable environmental conditions
o These genotypes lead to different phenotypes as light intensity varies, which is phenotypic plasticity
Another example is of Yarrow (Achillea) morphology in response to elevation

• They took plants with the same genotype and put them in 3 different elevations, the height and the form of the plant varies due to environmental differences
  o The plant varies according to phenotype
  
• In another experiment, plants with different genotypes were taken
  and placed at the same elevation/environment, there were differences in the height and form due to genetic differences
  

o The plant varies according to genotype • Norms of reaction:
o If norms of reaction aren’t parallel, then there is a Gene x Environment interaction
▪ There is a variation in plasticity among genotypes
▪ The slopes of the lines are different
o Two different genes were viewed according to their
plasticity

• ▪  Higher plasticity means that there is a lot of
  variation in the phenotype across environments • Gene1
  
• ▪  Lower plasticity means that there is not a lot of variation in the phenotype across environments
  • Gene4
  

• This type of variation can evolve since there is genetic variation
which links to the phenotypic variation and the type of response to the environment can depend on the genotype
Fitness Effects of Mutation:

• Gene: is a section of DNA that codes for a distinct RNA or protein product
  
• Locus: is a location of a gene on a chromosome
  
• Alleles: are versions of the same gene that differ in their nucleotide sequence
  
• Mutation: is the change in the nucleotide sequence of DNA
  Genetic Variation and Fitness:
  

• Point Mutation: is the single base change in DNA sequence, which gives rise to new alleles
o It is a common source of genetic variation o It can have large effects on the phenotypes
▪ Even mutations in introns can affect the proteins
• Introns: are the portion of the gene that don’t code for protein

products, yet they can affect the final protein ▪ Random errors in DNA replication

o Causes:
▪ Damage or chemical alteration to DNA

• For example, UV light or chemicals ▪ Lack of repair, example by DNA polymerase
• DNA polymerase: is a protein that repairs mistakes in the DNA o Examples of point mutations are:
▪ Sickle-cell anemia:
• Which is the single base substitution of hemoglobin gene
▪ AVIPAV
• 3 point mutations of 333 base pairs
• Indels:
o Is the insertion or deletion of nucleotides in DNA sequence
o There is a higher frequency in introns than in extrons in the genome o It can shift condon reading frame
▪ It changes the meaning of all downstream codons o Causes:
▪ Misalignment of DNA during replication
• This is common in regions with repeated base pairs
▪ Lack of repair by DNA polymerase o Examples:
▪ Huntington’s disease:

• Is a progressive brain disorder
  
• It is autosomal dominant and manifests in adults
  
• It is caused by insertion of many copies of C-A-G triplets in the
  HTT gene
  Genetic variation: there are 2 ways to measure it:
  

• Polymorphism: is a fraction of genes in a population with at least 2 alleles o Doesn’t look at the total number of alleles
  
• Mean heterozygosity (H): is the mean percentage of individuals who are heterozygous per locus
  o It is also the fraction of genes that are heterozygous in genotype of an average person
  Differences between polymorphism and heterozygosity:
  
  • For example, there are 2 loci (A and B)
    o In this population of 3 individuals, at locus A there
    could be AA and BB. At locus B, there could be aa and bb.
    ▪ Since there are 2 different alleles at each locus the polymorphism is 100%
    ▪ The mean heterozygosity = (1/3)*(1/2) = 17%
    
  • Variation among individuals can be measured based on allozyme electrophoresis, which
    is the electrophoresis analysis of variation in enzymes
    

o Based on phenotypic analysis, the mean heterozygosity is 4 – 15% of loci ▪ The enzyme loci polymorphic is 33 – 50%
• Example of genetic variation:
o The CFTR gene is a locus that is in cystic fibrosis.
o When they analyzed over 15 000 patients, the 1400 different mutations at this one
locus cause the same phenotypic effect, which is cystic fibrosis
• Conclusion: there are many alleles for many genes in most populations, which indicates
high polymorphism
o Mutations then do indeed generate new alleles in every generation
Fitness:

• The effect of mutations on individual fitness can range from: o Deleterious
  o Neutral
  o Beneficial
  
• Most mutations are
  deleterious
  
• Many mutations are
  neutral
  
• Beneficial mutations are
  rare
  How can mutations be neutral to fitness?
  
  • Silent site (synonymous) substitution:
    o Point mutation that doesn’t result in amino acid change
    o There is no change in protein, which means there isn’t a change in the phenotype
    (neutral)
    
  • Replacement (nonsynonymous) substitution:
    

o A point mutation occurs which results in an amino acid change
o This may not significantly affect the protein function if new amino acids have a
similar chemical property to the original
Are most mutations beneficial, neutral, or deleterious?
• Caenorhabditis elegans reproduce asexually. In this experiment, one of them produced 74 genetically identical lines, which then went through 214 generations of reproduction
o There was no natural selection
o There was optimal conditions for growth and reproduction
o They also randomly selected the single parent for each generation
o It then became 74 mutation accumulation lines
o The graph showed that the accumulation of mutations resulted in a decrease in
fitness of 0.5% per generation

• In another experiment, they did it with controls in a lab.
  o In each generation, there was competition for resources
  o There were large groups of parents were chosen randomly from survivors o There were 74 control lines
  
• Most mutations are at least mildly deleterious, but some are beneficial. o When natural selection was reintroduced, they recovered
  
• In another experiment, they tracked the effect of mutation on a single gene in Brewer’s yeast
  

o The HSP90 wild type gene was used which increases fitness at high temperatures o In the initial population of yeast, there were 560 different single based mutations
and individuals
o They allowed the cells to compete with the wild type
o They then measured the fitness as relative frequency of the cells o Majority of the mutations are deleterious

BIOB51 – Lecture 8 Variation and Mutation: Mutation Rates:


• 50 independent lines are reproduced from a certain organism, and then 396 generations of reproduction are watched.
o There is no natural selection and there are benign conditions
o There is also a random selection of single parent each generation
o This leads to approximately 50 mutation accumulation lines
o This is similar to the other experiments previously looked at but this one directly
compares the DNA sequence changes over the period of time
▪ There was an average of 2.1 mutations per genome per generation
• You can do direct measurements based on gene sequencing, even for humans and their genomes
o They took genetic information from human parents and their offspring o A new mutation showed up in the offspring
o Most individuals carry approximately 60-180 new alleles
o About 10% of these are phenotypically detectable
Mutation rates vary:

• Across species
  
• Across regions of the genome
  
• Between sexes
  
• Between families
  
• The mutation rate on the graph per base pair per generation is low
  o The mutation rate increases with genome size in cellular organisms
  
• The mutation rate per base pair per generation is high in viruses
  o The mutation rate decreases with genome size in non-eukaryotes Evolution of Mutation Rate:
  

• Evolution by natural selection requires: o Variation
o Heritability of variation
o Fitness differences of heritable phenotypes

• Mutation rates depend on the accuracy of DNA polymerase, which is for replication and
  repair
  
• It also depends on the accuracy of DNA polymerase which varies due to allelic variation
  Effect of decreased effectiveness of DNA polymerase:
  

• In an experiment, they looked at different types of mice who were genetically engineered to carry copies of certain alleles:

o The wild type o Deficient
▪ Had one allele with a low function o Double deficient
▪ Two alleles with a low function

• The mutation rates increased as the number of deficient alleles increased
  
• The mortality rates due to cancer increased as well
  
• This experiment indicated that mutation rates can evolve if some DNA polymerase
  variants confer higher fitness than others in certain environments
  Is there selection on mutation rates?
  
  • There is a trade-off between speed and accuracy of DNA replication
    
  • The faster the developing base pair is made, the more likely it is that the DNA
    polymerase won’t recognize and fix the errors
    Fitness Effects on Mutation:
    
    • The study of Brewer’s yeast showed that at hot temperatures, the gene increased fitness
      
    • Most of the mutations are considered to be deleterious at 36 degrees
      o The HSP90 gene is an adaptation for high temperatures
      
    • They also took the same amount of base pairs and did the experiment at a lower
      temperature (25 degrees)
      o This resulted in the gene being less effective
      o Most mutations are either neutral or deleterious
      
    • The fitness effect of mutation depends on the environment Mutation rate and the environment:
      

• Hypothesis: the effect of the mutation rate on fitness depends on the environment
o High mutation rates favoured in novel (different than their regular environment)
or rapidly changing environments since the organism is not adapted to current
conditions
o Low mutation rates favoured in familiar or stable environments

• ▪  The organism is adapted to current conditions
  
• ▪  In the mutation accumulation experiment, most mutations tended to
  decrease fitness
  High mutation rate in new environment:
  

• Experiment 1: effect of novel environment: o Uses 2 different strains of E.coli:
▪ Mutator: has high mutation rates
• This is due to mutation in mismatch-repair system, which is a
strain that shows high rates of all genetic mutations
▪ Wild type (wt)

o The equal number of E.coli is injected into separate, anti-biotic-treated experimental mice, in a novel environment
o The fitness of each strain is examined by assessing bacterial counts in fecal samples
▪ The larger the bacteria load in the body, the more bacteria in the feces. o The results showed that the mutator strain is more successful during early
infection, which is with the first 15 days
o When the wild-type strain adapts after 15 days, the mutator advantage is lost
• Experiment 2: competition in novel environment:
o The mutator and wild-type strains are injected into the same mice at different
initial ratios
▪ There is a novel environment and there is direct competition at different
levels between the cells
o The relative fitness of each strain is examined by assessing the ratio of each strain
in fecal samples
o In the graph, when the log axis is a positive number it indicates that the mutator is
present in the feces at a higher frequency than of the wild type
o If there is a negative number, then it shows that the wild type is present at a higher
frequency than the mutator
o The frequency of the mutator increases relative to the wild-type o Mutator: has an overwhelming advantage in competition
▪ This is because a beneficial mutation will spread quickly throughout the population
o Mutator advantage: is maintained when the initial inoculation gives numerical advantage to the wild-type
▪ This stays until the wild-type inoculation is so large that the significant number of beneficial mutations is likely in wild-type
• Conclusions:
o Higher mutation rates are favoured in novel environments. There is an increased
probability of novel traits that are well suited to the new environment, or can win over the competition
▪ This allows more rapid adaptation to new conditions • For example, the bacteria in experiment 1
▪ This gives an advantage in competition
• For example, the bacteria in experiment 2
o Higher mutation rates are costly in constant environments
▪ For example, C elegans experiment, HSP90 mutation at high temperatures ▪ Mutation usually decrease adaptations
Mutation Rate, Growth Rate, and Environment?
• When might a high mutation rate be beneficial?
o This occurs when there is a novel environment, which has abiotic conditions and
competitors

• When might rapid replication be beneficial? o For example,
▪ HIV (human immunodeficiency virus) in RNA:

• It infects human white blood cells
  
• It causes infected cells to attack other immune system cells, which
  

Summary of Mutation:

compromises the immune system response

• HIV infected cells can be destroyed by the immune system if it
  recognizes proteins produced by the virus
  
• High mutation rate in HIV gives a constant change in proteins,
  which is difficult for the host to recognize infected cells
  
• Rapid replication of HIV gives more virions will be released
  before the cell is destroyed by the immune system
  
• The error rate in HIV replication is about:
  o 1000 x higher than the error rate in typical influenza rate o About 1 000 000 x higher than the error rate for DNA
  replication in humans
  

• The source of variation in populations:
  o The most common type of mutation is point mutation which creates new alleles o A lot of genetic variation exists
  
• Mutation rates are variable and can evolve. There is selection for: o Low mutation rates in stable environments
  o High mutation rates in novel/changing environments
  
• Most mutations are mildly deleterious in stable environments; beneficial mutations are rare
  
• The likelihood of a new beneficial mutation arising in a population depends on: o The mutation rate
  o The population size o The time
  Genetic Variation and Fitness:
  

• Why doesn’t natural selection remove most genetic variation from populations?
o Mutations add new genetic variants at every generation
o The genotype linked to the most fit phenotype may vary. For example, genotype x
environment
o Mutation provides heritable variation that is essential to evolution
Definitions:
• Evolution: changes in allele frequencies for a given trait in a population over time o Mutation: is a mechanism of evolution
▪ However, does it alone cause significant change in allele frequencies?

• ▪  Mutation alone isn’t a potent evolutionary force
  
• ▪  Although mutation can make new alleles and is necessary for evolution to
  occur, it doesn’t change allele frequencies, which is random and rare
  
  • It is random because mutations are equally likely at every locus
    
  • It is rare because the mutation rate per locus is low
    
• ▪  Thus, the likelihood that many individuals produce gametes with the same mutation in one generation is very low